The purpose of the present investigation is to study the regulation of the pulmonary circulation by a multidisciplinary approach. Pulmonary vascular responses to a wide variety of vasoactive hormones will be investigated in the intact dog, cat, monkey, swine and lamb. New techniques for perfusion of a lung lobe in the intact spontaneously breathing cat and monkey are being developed. The effects of prostaglandin precursors, prostaglandin intermediates and primary prostaglandins will be contrasted in the feline, canine and monkey pulmonary vascular bed. Arachidonic acid, the prostaglandin precursor, PGE2, PGF2 alpha and an analog of the endoperoxide PGH2, all increased pulmonary vascular resistance in the dog by constricing intrapulmonary veins and upstream vessels in a dose-related manner. The response to 10 micrograms PGF2 alpha, was approximately equal to 100 micrograms PGE2 and 1000 micrograms arachidonic acid. The PGH2 analog was 10 times more active than PGF2 alpha. The response to AA was associated with a 2 to 3-fold increase in levels of PGE2 and PGF2 alpha in pulmonary venous blood as measured by radioimmuno assay. The response to arachidonic acid was blocked by indomethacin, an inhibitor of prostaglandin synthetase. Intravascular platelet aggregation was not identified by light or electron microscopy. Hypoxia inhibited the response to arachidonic acid whereas endotoxin enhanced the response to the prostaglandin precursor. These data show that prostaglandins, intermediates and precursors all have marked activity on the canine pulmonary vascular bed. The present data suggest that the pulmonary vascular response to arachidonic acid is due to the effects of both intermediates (endoperoxides) and PGE2 and PGF2 alpha. In addition, these results demonstrate that altered physiologic or disease states may modify the activity of both prostaglandin synthesizing and metabolizing enzyme systems in the lung. BIBLIOGRAPHIC REFERENCE: Hughes, J.P., Kadowitz, P.J., Hyman, A.L., Ray, J.E. and Joiner, P.D. Pharmacology of human isolated colonic circular and longitudinal smooth muscle from cancer and non-cancer patients. Diseases of the Colon and Rectum. 19:120-125, 1976.